2018 Fiscal Year Annual Research Report
Determination of the functions of specific CD44 proteins in human skin and epidermis and their relation to skin diseases, cancer and autoimmunity
Project/Area Number |
16K10137
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Research Institution | Kurume University |
Principal Investigator |
TEYE KWESI 久留米大学, 皮膚細胞生物学研究所, 助教 (30599303)
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Co-Investigator(Kenkyū-buntansha) |
橋本 隆 久留米大学, 皮膚細胞生物学研究所, 教授 (20129597) [Withdrawn]
名嘉真 武国 久留米大学, 医学部, 教授 (50221453)
沼田 早苗 久留米大学, 医学部, 助教 (40599312)
石井 文人 久留米大学, 医学部, 准教授 (80330827)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Keywords | CD44 / Squamous cell carcinoma / Human Skin Keratinocyte / Skin Cancer / Skin disease |
Outline of Annual Research Achievements |
We studied the functions and potential roles of CD44 proteins in human skin. We for the first time identified up to 18 transcripts of CD44 in human skin epidermal keratinocytes and studied their roles in normal and disease skin development. To gain insight into CD44 function, we performed immunostaining of normal skin and various skin diseases. We found that CD44 variant expression tend to be reduced in various skin cancers, particularly squamous cell carcinoma but not in inflammatory diseases such as psoriasis and atopy dermatitis. Using a keratinocytes cell line, we have been able to completely knock-out CD44 by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system through homology directed repair (HDR) and the cells expressed no CD44. To gain insight into pathways controlled by CD44, we performed Micro-array analysis using RNA from CD44 wild type and CD44 knockout cells. We found several genes that are controlled by CD44 proteins. Some important genes are either up- or down-regulated. Particularly, we found that knockdown of CD44 led to reduced expression of all 3 subunits of a certain laminin, which is important for maintaining structural integrity of human skin. We confirmed that the protein level is decreased in the cells. Furthermore, we were able to establish keratinocyte cell lines expressing a specific CD44 molecule. These cells will be useful for identifying which CD44 protein have a particular function, because each CD44 molecule is thought to have a unique function. Our study revealed important functions of CD44 in human skin.
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Research Products
(7 results)
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[Journal Article] Clinical and Immunological Study of 30 Cases With Both IgG and IgA Anti-Keratinocyte Cell Surface Autoantibodies Toward the Definition of Intercellular IgG/IgA Dermatosis2018
Author(s)
Hashimoto T, Teye K, Hashimoto K, Wozniak K, Ueo D, Fujiwara S, Inafuku K, Kotobuki Y, Jukic IL, Marinovic B, Bruckner A, Tsuruta D, Kawakami T, Ishii N.
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Journal Title
Frontiers in Immunology
Volume: 9
Pages: 994
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Unusual CD44 form in epidermal differentiation.2019
Author(s)
Kwesi Teye, Hiroshi Koga, Norito Ishii, Sanae Numata, Takashi Hashimoto, Marek Haftek, Takekuni Nakama,
Organizer
Gordon Research Conference (GRC) on Barrier Function of Mammalian Skin.(Waterville Valley, NH, USA, August 11 - 16, 2019)
Int'l Joint Research / Invited
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[Presentation] Filaggrin gene (FLG) promoter polymorphisms are associated with atopic dermatitis but not ichthyosis vulgaris in Japan,2018
Author(s)
Kwesi Teye, Hiroshi Koga, Akira Nagai, Chika Ohata, Sanae Numata, Norito Ishii and Takekuni Nakama,
Organizer
IID2018, Orlando, Florida,(May 16-19, 2018)
Int'l Joint Research